A comprehensive description about Emulsions from Industrial Pharmacy by Lachman.

1. Emulsions
8th semester

2. Course outlines
• Emulsion stability
• Mechanical equipments
• Specific formulation condiderations

3. Emulsion
• Emulsions
• Why needed (Advantages+Disadvantages)
• Classification

4. Emulsion
Derived from latin word- to milk
Emulsion is a biphasic liquid system consisting of two or more liquids that are
normally immiscible and one phase is dispersed as a minute globules in another.
It is thermodynamically unstable system which gets stabilised by adding
emulsifying agent.
How droplets get stabilized by the addition of Emulsifier?
Emulsifier form intefacila film thus
• reduces interfacial tension
• Provide mechanical barrier and avoaid coalescence
• Provide electric barrier so that droplets don’t approach

5. Emulsions
EMULSIFYING AGENTS
• Emulsifying agents are substance that are soluble in both water and fat and enable
fat to be uniformly dispersed in water as an emulsion.
Emulsifying agent prevent coalescence of globules by forming film around globules.
• An emulsifying agent is any material that enhances the stability of an emulsion.

6. Emulsions-why needed
ADVANTAGES
• Medicines having an unpleasant taste and order can be made more palatable for oral
administration in the form of an emulsion.
• For Sustained release medication.
• Suitable for both lipophilic and hydrophilic drugs
• Cost effective
• Emulsions protect drugs against oxidation or hydrolysis.
DISADVANTAGES
• Emulsions are less stable.
• They are susceptible to microbial growth.
• Packing, handling & storage is difficult.
• have short shelf life.
• Leads to creaming (upward movement of dispersed globules) & cracking (separation of
two phases)
• Leads to phase inversion.

7. Emulsions
Daily life exp
Milk o/w
Mayonnaise o/w
Margarine w/o
Sauses, paint o/w
Pharmaceutical emulsions
1. Cremaffin (Magnesium hydroxide mixture + liquid paraffin
Laxative emulsion for constipation relief byAbbott
2. Cationorm (Mineral oil)
Eye emulsion for dry eye relief by Santen

8. Emulsions-Classification
1. On the base of dispersed phase
• o/w
• w/o
2. On the base of globule size
• Macro emulsion (more than 50 µm)
• Micro emulsions (100-600 nm)
• Nano emulsions (below 100 nm)
3. On the base of mode of application
• Emulsions for oral administration (for oral use eg: Fish liver oil emulsion)
• Emulsions for external use (Lotions, creams and liniments)
• Emulsions for parenteral use (o/w emulsions of nutritive oils and fats andVitamin K that
prevents blood clot)
• Emulsions for rectal use (Semi-solid emulsions. w/o type semi-solid emulsions are oily
creams while o/w semisolid emulsions are aqueous creams)

9. Emulsions- Difference

10. Emulsions
Microemulsions
• Clear, stable, liquid mixtures of oil, water and surfactant, frequently in
combination with a co-surfactant
• In contrast to ordinary emulsion, Microemulsions form upon simple mixing of
the components and do not require the high shear conditions generally used in
the formation of ordinary emulsions.
• Unlike the common macro emulsion in that:
1- Appear as clear transparent solution.
2- Diameter of internal phase droplets ranged between 100- 600nm.
3-Thermodynamically stable.

11. EMULSION STABILITY

12. EMULSION STABILITY
Two types of stabilities are important
• Thermodynamic stability (related with temp and mechanical energy)
Surfactant/ emulsifier lowers the interfacial tension between the oil and water. This
facilitates the formation of droplets during emulsification and reduces the
thermodynamic tendency for coalescence.
• Kinetic stability (related with position/ dispersed or hanging state of globules)
As emulsifier increases the viscosity of emulsion, thus restrict the motion of
globules and maintains the dispersion state of emulsion for extended period of
time.

13. EMULSION STABILITY
Stability:
Resistance to the change in properties (physical/chemical) over period of time.
Why we check stability
• Predicts shelf life
• Assure the quality of product (form mfg - patient use- expiry)
Products checked for
• Original appearance
• Odour
• Consistancy
• Microbial growth

14. Stability problems
Physical stability problems
• Creaming (reversible)
Subtle formulations(Microscopically visualised)
• Flocculation (reversible)
• Coalescence (irreversible)
(Large globules-Phase separation)
• Ostwald ripening (irreversible)
• Phase inversion (Special case)
May or may not be in order
Not independent (each influence other and get influenced by other)
Chemical stability
problems
• Oxidation
• Hydrolysis

15. EMULSION STABILITY
Chemical instability
A product is said to be chemically instable if there is a change in chemical
property of formulation components.
Oxidation (addition of O2 due to reaction with atmospheric O2)
Hydrolysis (Chemical breakdown of compound due to reaction with H2O)

16. EMULSION STABILITY
Oxidation
Selection criteria:
• No compatibility b/w formulation components
• Suitable selection of oil (Oils tend to oxidize with atm. O2 and microbial
contamination)
• Resultantly rancidity produces (Foul odor and taste)- reduces shelf life
How to overcome
• By adding anti oxidants
• Preservatives

17. EMULSION STABILITY
Hydrolysis
Selection criteria:
• Suitable selection of Emulsifiers (some polymers are more liable to
hydrolysis- microbial growth)
• Compatibility of formulation components (non ionic E.A interfere
with phenolic preservatives to form hydrogen bonding)
• Resultantly poor function of preservative and E.A as well- reducing
shelf life
• Anionic E.A (-ve) SLS interact with cationic drug (+ve) neomycin
reduces required repulsion force- destroy structure of external
phase.

18. EMULSION STABILITY
Physical instability
1. Creaming (Reversible)
It is a process which occurs when the dispersed droplets
separate under the influence of gravity to form a layer of
more concentrated emulsion, the cream.
• Aggregation of globules on top or bottom according to
density difference
• Upward (o/w)
• Downward (w/o)
• Governed by stockes law Cr= R2(ρc−ρo)/ηc
R= radius , ρc= density cont phase, ρo= Density of disperse
phase, ηc=Viscosity

19. EMULSION STABILITY
Creaming
Reasons (from equation)
• If emulsion contains large droplets of dispersed
phase.
• If emulsion is dilute (less viscosity).
• If there is a density difference between the oil and
water phases.
How to overcome
• Small droplet size.
• Increase viscosity of external phase.

20. EMULSION STABILITY
2. Flocculation (Reversible)
It is a weak, reversible aggregation of droplets of the internal phase in the form of clusters.
• Rapidly settle down under the influence of gravity than in creaming
• Individuality of globules remains intact- each cluster serve as a single kinetic unit
Reasons
• Wander vaal attraction + electrostatic replusive forces
• High internal phase volume ratio
• Excess of electrolytes
• Excess of emulsifier
• High viscosity-high floccule and vice versa
How to overcome
• By attaching charge species of similar charges (high repulsion, low attraction b/w floccule)

21. EMULSION STABILITY
3. COALESCENCE AND CRACKING (irreversible)
The process in which dispersed phase globules merge to form larger
droplets.
• The process will continue until the emulsion breaks (cracks in
globules) and there is complete separation of the oil and water
phases.
• Break/ larger sized- individuality doestnot remain intact
Reasons
• Poor or low emulsifier-(low mechanical+electrical barrier)
• Chemical interaction
How to overcome
• Suitable amount of E.A (Thick interfacial film)

22. EMULSION STABILITY

23. EMULSION STABILITY
3. Ostwald Ripening (irreversible)
Enlargement of particle size on storage
Growth of large droplets at the expense of smaller ones.
Large becomes larger, small becomes smaller (more soluble)- join to
large globules to make bigger ones
Reasons
• Soulbility difference of globules
• Smaller globules more soluble
• Leads to Phase separation
How to overcome
• Prevented by Continuous shearing
• By increasing the viscosity of external phase

24. EMULSION STABILITY
4. Phase inversion (irreversible)
The process in which an emulsion changes from one type to
another, for example o/w to w/o.
Under specific conditions
Reasons
• amount of disperse phase exceeds a theoretical
maximum of 74% of the total volume.
• If the emulsifier solubility is changed under temperature
• Interaction with additives eg. Divalent ions (Na,Ca)

25. Stability studies/Evaluation of dosage forms
1) RealTime stability testing
• Long term, under recommended conditions.
• Data collection periodically.
2) Accelerated stability testing
• Testing under extreme conditions.
• Temperature, light, agitation, gravity, pH, humidity.
• Temperature: 4 ⸰C, 25 ⸰C, 37 ⸰C and 40 ⸰C.
• To increase the rate of degradation.
• Based uponArrhenius theory.
• Arrhenius concept: 3X increase in rate of degardation upon 10 ⸰C.

26. Stability studies/Evaluation of dosage forms
3) Retained samples stability testing
• Samples collection from market
• < 50 batches, samples from single batch.
• >50 batches, samples from 2 batches.
• If shelf life 5 years sampling time: 3,6,12,18,24, 36,48 and 60
Months.
4) Cycle temperature stress testing (rare)
• Keep at specific temperature 24 h.
• At least 20 cycles

27. EMULSION STABILITY
Stress conditions/ Accelerated stability for emulsions
• Aging and temperature
Cycling between 4 ⸰C and 45 ⸰C
creaming, coalescence
viscosity change (thick on cooling, thin on warm temp)
Freezing damage more (alter the solubility of E.A, ice crystal may deform spherical structure
by applying pressure)
• Centrifugation
Phase separation
↑ gravity ↑ phase separation.
Centrifugation at 3750 rpm for 5 h= effect of gravity for 1 year.
• Agitation (Specific and designed way)
Mechanical oscilation
Butter from milk

28. EMULSION STABILITY
Monitoring for following characteristics/Parameters
• Change in electric conductivity (conductivity meter)
• Phase separation (Visual/measure volume of separated phases)
• Measure zeta potential (Zeta sizer)
• Change in odor/taste/color (visual/organoleptic)
• Change in pH (pH meter)
• Change in viscosity (Viscometer)
• Change in particle size (Image analysis, microscopic examination SEM)
• Change in light reflection (high transmittance-small particle size)
• Change in active ingredient (Bio assay)
• Preservation (Microbial assay)

29. EMULSION STABILITY
Practical recommendation for shelf life prediction
or
Characteristics of Stable emulsion (Acceptable emulsion)
Emulsion should stable (no signs of separation)
• 3 months at 45 ⸰C or 50 ⸰C (Elevated temp)
• 6 months at 37 ⸰C (Elevated temp)
• 12-18 months at 25 ⸰C (Ambient temp)
• 1 months at 4 ⸰C (Refrigerator)
• 2-3 freeze-thaw cycle between -20 ⸰C and 25 ⸰C
• 6-8 heating-cooling cycle between 4 ⸰C and 45 ⸰C (each cycle for 48 h)
• Stable by centrifugation at 2000-3000 rpm at room temp.
• Stable by agitation on reciprocating shaker (24-48 h)
• No significant change in microbial assay and in bio assay (Active ingredient).

30. Mechanical Equipments

31. Mechanical Equipments
Various types of equipment are available either in laboratory or in industries:
1. Mechanical stirrers
2. Homogenizers
3. Ultrasonic Devices
4. Colloid Mills
Shear force: cutting or breaking down of internal phase into droplets under speed
and pressure (agitation+turbulance)
Factors affecting:
• Diameter of nozzle
• Speed of liquid injected
• Density and viscosity of liquid injected
• Interfacial tension at interface b/w liquids

32. Mechanical Equipments
SELECTION OF EMULSIFICATION EQUIPMENT
depends on a number of inter-related factors:
• The oil used
• The volume of emulsion to be prepared
• The type of emulsifier used
• The range of droplet sizes required
• The flow properties of the emulsion during the emulsification and cooling
processes - Phase to volume ratios
• The desired physical properties of the product

33. Mechanical Equipments
1. Mechanical stirrers
• For low to moderate viscosity emulsions
• Not suitable for micro/nano emulsions
An emulsion may be stirred by means of various impellers mounted on shaft which are placed directly into system to be
emulsified. (They control pressure (suction) and speed (flow) of liquid)
I. SHAKER MIXERS
CONSTRUCTION • A vessel and an oscillator or rotator.
WORKING • In these mixer material is placed in the vessel and is agitated by either by an oscillator or rotary movement.
Shaker mixers have limited use in industries.
II. PROPELLER MIXERS
CONSTRUCTION • A container • Shaft • Propeller and strips (push forward)
WORKING
• The size of the propeller is very small as compared to container
• It rotates at very high speed up to 8000 rpm.
• Propeller mixers are the most widely used form for liquid of low viscosity.
• Not suitable for viscous liquids like glycerin, liquid paraffin etc.
• Propeller mixers are suitable for routine laboratory and production purposes

34. Mechanical Equipments
III.TURBINE MIXERS
CONSTRUCTION • A circular disc impeller (suction) • Blades • Containers
WORKING
• Flow pattern- Radial, axial and tangentinal flow
• These mixers are rotated at lower speed than propellers
• It produces greater shear forces.
• They are used for special application in the preparation of emulsion of high or moderate
viscosity. If more vigorous agitation is required, they are used.
IV. PADDLE MIXERS
CONSTRUCTION • Number of paddles •Vertical shaft • Flat blade • Container
WORKING
• A number of paddle mixers having different shapes and sizes depending on the nature and
viscosity of the product .
• The blades have a large surface area in relation to container. Blades help them to rotate close to
the walls of container and effectively mix the viscous liquids and semi-solids.They rotate at
speed of 10 rpm or less.

35. Mechanical Equipments
2. Homogenizers
Principle Homogenizers are based on the principle that large globules in
coarse emulsion are passed, through a small inlet orifice at high pressure is
broken into smaller globules having a greater degree of uniformity and
stability.
• Emulsion can be recycled through the homogenizer more than once.
• There are different designs of equipment (for liquid & pastes) and
homogenizer raises temperature of emulsion so cooling is required.

36. Mechanical Equipments
SILVERSON MIXER HOMOGENIZER
• Fast and efficient
• May produce droplets of 2-5 microns
• Principle on high shear mixing
• Reduces mixing time up to 90% than conventional methods
CONSTRUCTION • Motor •stand •Shaft •Emulsifying head
WORKING
• The emulsifying head is adjusted in such a way that it is immersed in the liquid to be
emulsified.The head is rotated at high speed with motor.
• The liquids are powerfully sucked through fine mesh into the blade of emulsifying head
where they are subjected vigorous mixing by high speed rotating blades.
• The material is then expelled radially and forcefully through sieve hand.
• In this way whole of the liquids to be mixed are made to pass repeatedly through
emulsifying head and large globules are converted to small globules.

37. Mechanical Equipments
Figure: Silverson mixer homogenizer

38. Mechanical Equipments
3. Ultrasonifiers
By using ultrasonic energy
WORKING
• The dispersion is forced through orifice at a modest pressure and is
allowed to impinge upon vibrating blade.
• The pressure required is in range of 150-350 psi and can cause the
blade to vibrate rapidly and produce ultrasonic note.
• Applied for emulsions for moderate viscosity and low particle size

39. Mechanical Equipments
4. COLLOID MILLS
PRINCIPLE
• Homogenizer and ultrasonic equipment depend on sudden changes in pressure to effect
dispersion of liquids.
• Colloid mills operate on principle of high shear only which is generated between motor and
stator.
CONSTRUCTION • Hopper/Inlet • Rotor • Stator •outlet
WORKING
• It consists of motor, conical rotor and stator.
The gap between them can be adjusted from 0.002-0.03 inches .
• Rotor is connected to high speed motor which can revolve at speed of 3000-20000 rpm.
• Previously grounded material is fed into machine with hopper and it is thrown outward by
centrifugal action.
As the material passes through a narrow gap between rotor and stator, size is reduced.

40. Mechanical Equipments
ADVANTAGES
• Products with particle size less than 1µm
• Useful for preparing pharmaceutical syrup, emulsion,
lotions, ointments,creams and semi solids.
• Size reduction is always carried out in presence of liquid.
DISADVANTAGES
• Not applicable for processing dry material.
• Materials need to be milled previously.

41. Formulation Considerations

42. Formulation Considerations
Thermodynamically unstable system → separate oil and water phases (i.e. crack) by
coalescence → EMULSIFIER →Kinetically stable →dispersed state
Normally water attracts other water molecules and repell by oil phase
↑immisibility ↑ interfacial tension ↓ contact area between dissimilar molecules
↑creaming
E.A (amphiphilic) act as stabilizer to globules of internal phase
Mechanism/Function of E.A
1. ↓ of interfacial tension at interface
2. Interfacial film---mechanical barrier to coalescence
3. Electrical repulsion --- electric barrier to approach particles
4. Rheological barrier to prevent coalescence (↑viscosity of ext. phase ↑kinetic
stability)

43. Formulation Considerations
Type of emulsion + droplet size distribution
Method of preparation of emulsion
Relative volumes of water and oil phases (Phase vol ratio)
Chemical nature of emulsifying agent (dominance of polar/non polar character)
Polar/ionic head -------------non polar/hydrocarbon tail

44. Formulation Considerations

45. Formulation Considerations
HLB value
Charged surfactants (more polar)-----O/W (sodium and potassium oleates)
Surfactants low dissociate--------------W/O (calcium and magnesium soaps)
Non ionic sorbitan esters--------------------W/O
Hydrophilic sorbitan esters-----------------O/W

46. Formulation Considerations
FORMULATION COMPONENTS
The Choice of Formulation components will depend on:
- Emulsion type (o/w, w/o or multiple emulsion)
- The route of administration
- Clinical use
- Cost and Compatibility of Ingredients
The Processing conditions are also optimized as they control:
- Droplet size distributions and Rheological properties.
- Droplet size of internal phase of emulsion and consistency of emulsion
influence emulsion stability and its therapeutic response because the
smallest the globule size, greater will be the absorption

47. Formulation Considerations
FORMULATION COMPONENTS
• Aqueous phase • Oil phase
• Emulsifying agent • Preservatives
• Antioxidants • Flavourant for Oral Emulsion
• Fragrance for cosmetic emulsion

48. Formulation Considerations
OIL PHASE
Oil may be the medicament itself or may be used as carrier for some lipid
soluble drugs.
CONSIDERATION FOR OIL PHASE
•The desired physical properties of Emulsion (liquid/Semi solid)
•The miscibility of the oil and aqueous phases
•The solubility of the drug in the oil (↑solubility ↑absorption skin/GIT)
•The desired consistency of final emulsion (liquid,cream,lotion)
(fluid emulsion-↓ internal phase)
(Thick emulsion- ↑ internal phase ↑E.A)

49. Formulation Considerations
FOR ORAL EMULSIONS
The selection of oil phase depends upon the purpose or the product.
E.g. Castor oil and mineral oil are used as laxative
Fish liver oil and arachis oil are used as nutritional supplements
FOR EXTERNAL EMULSIONS
Oils based on hydrocarbons are widely used.
E.g. Liquid paraffin, soft or hard paraffin. Similarly turpentine oil and various silicone
oils are also used.
Also consider Greasy/non greasy texture—consumer acceptance
FOR PARENTERAL EMULSIONS
A range of purified vegetable oils have been used over many years in emulsions for
parenteral nutrition and as lipid soluble drug carriers.
E.g. refined fish oils, purified olive and soya oils.

50. Formulation Considerations
EMUISIFYING AGENT
The choice of emulsifier depends on many factors, these include:
- Type of emulsion to be prepared (hydrophilic E.A forO/W vice verca)
- Emulsifier toxicity or irritancy
- Clinical use of emulsion
- Shelf life of emulsion (stable to heat/ storage)
- Cost and availability

51. Formulation Considerations
ANTI MICROBIAL PRESERVATIVES
An ideal preservative should:
Exhibit a wide spectrum of activity against bacteria and fungi
Nontoxic and non irritant
Be stable to heat and storage
Chemically compatible (e.g. polyoxyethylene nonionic surfactants and
phenolic preservatives are incompatible)
Have reasonable cost
Have acceptable taste, odor and color.
- Examples: phenoxyethanol, benzoic acid and the p-hydroxybenzoates.

52. Formulation Considerations
ANTIOXIDANTS
Organic compounds/lipids/drugs---auto oxidation---decomposition
Antioxidants prevent oxidative deterioration of the oil, emulsifier or the drug itself
during storage.
•The antioxidants commonly used in pharmacy include
Butylated hydroxy anisole + butylated hydroxytoluene up to 0.2%
Alkyl gallates, which are effective at very low concentrations (0.001% to 0.1%).
L-Tocopherol is added to some commercial lipid emulsions to prevent
peroxidation of unsaturated fatty acids.

53. Formulation Considerations
OTHER EXCIPIENTS
• Humectants (Hydrants) are often added to dermatological preparations to
reduce evaporation of water from the emulsion during storage and use.
E.g. propylene glycol, glycerol and sorbitol at concentrations up to 5% are
added.
• Other excipients for proper formation of emulsion are flavoring agent for
oral emulsions and fragrances for topical cosmetic emulsions.